Does vaginal progesterone reduce repeated miscarriage?

This review looked at whether progesterone as vaginal supplements can reduce repeated miscarriages. It found that for women with bleeding during pregnancy and a history of miscarriage, progesterone supplements may increase the birth rate.

Miscarriages are a concern to women with infertility. Roughly half of miscarriages are due to an abnormal number of chromosomes (pieces of genetic material), which occurs randomly. However, women who have had miscarriages of normal embryos are at increased risk of miscarriages in the future.

Low progesterone is a possible cause of repeated miscarriages. Progesterone is a hormone that supports a pregnancy. However, until recently, studies of progesterone supplements and miscarriage were small and not robustly designed. Two well-designed studies of progesterone vaginal supplements were published in 2015 and 2019. This review interprets what we know about progesterone vaginal supplements and repeated miscarriages in light of these studies.

This study analyzed data from two large trials evaluating vaginal progesterone in women with miscarriages.

The PROMISE trial studied 836 women with three or more previous miscarriages. Half the patients used vaginal micronized progesterone, and half used an inactive placebo gel. There was no clear difference in the birth rate between the two groups (66% for the progesterone group vs 63% for the placebo group). However, in women with more miscarriages, there was a trend toward a higher live birth rate with progesterone compared to placebo.

The PRISM trial studied 4153 women with bleeding during the first trimester. Half of the patients used vaginal micronized progesterone. There was a trend toward a slightly higher birth rate in the patients who used progesterone (75% vs. 72%). Among patients with one or two previous miscarriages, those taking progesterone had significantly higher birth rates (75% vs. 70%). Among the patients with three or more previous miscarriages, there was a significantly higher birth rate in those taking progesterone (72% vs. 57%).

This review found that progesterone vaginal supplements may increase birth rates for women with previous miscarriages and bleeding during the first trimester.